tbuckley/cabot-search huggingface dataset:
Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment
Authors: Daniel C. Javitt
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments. At the neurochemical level, acute administration of N-methyl-d-aspartate receptor (NMDAR) antagonists reproduces the pattern of neurocognitive dysfunction associated with schizophrenia, encouraging the development of treatments targeted at both NMDAR and its interactome. At the local-circuit level, an auditory neurophysiological measure, mismatch negativity, has emerged both as a veridical index of NMDAR dysfunction and excitatory/inhibitory imbalance in schizophrenia and as a critical biomarker for early-stage translational drug development. Although no compounds have yet been approved for treatment of cognitive impairment associated with schizophrenia, several candidates are showing promise in early-phase testing.
Endocrine Disorders and COVID-19
Authors: Seda Hanife Oguz, Bulent Okan Yildiz
Journal: Annual Review of Medicine (2022)

The multifaceted interaction between coronavirus disease 2019 (COVID-19) and the endocrine system has been a major area of scientific research over the past two years. While common endocrine/metabolic disorders such as obesity and diabetes have been recognized among significant risk factors for COVID-19 severity, several endocrine organs were identified to be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). New-onset endocrine disorders related to COVID-19 were reported while long-term effects, if any, are yet to be determined. Meanwhile, the “stay home” measures during the pandemic caused interruption in the care of patients with pre-existing endocrine disorders and may have impeded the diagnosis and treatment of new ones. This review aims to outline this complex interaction between COVID-19 and endocrine disorders by synthesizing the current scientific knowledge obtained from clinical and pathophysiological studies, and to emphasize considerations for future research.
Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination
Authors: Sarah F. Rosen, Allison L. Soung, Wei Yang, Shenjian Ai, Marlene Kanmogne, Veronica A. Davé, Maxim Artyomov, Jeffrey A. Magee, Robyn S. Klein
Journal: Genome Medicine (2022)

Abstract Background Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (T R M) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown. Methods Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss. Results Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in T R M cell biology, was identified as critically regulating CXCR6 expressing CD8 + T R M cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8 + T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 not only is required for the maintenance of WNV-specific CD8 T R M cells in the post-infectious CNS, but also contributes to their expression of T R M cell markers. Moreover, CXCR6 + CD8 + T cells are required for glial activation and ongoing synapse elimination. Conclusions We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8 + T cells that maintains forebrain T R M cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8 + T R M cells.
Flexor Tendon Tenotomy Treatment of the Diabetic Foot: A Multicenter Randomized Controlled Trial
Authors: Jonas Askø Andersen, Anne Rasmussen, Susanne Engberg, Jesper Bencke, Marie Frimodt-Møller, Klaus Kirketerp-Møller, Peter Rossing
Journal: Diabetes Care (2022)

OBJECTIVE The aim of this study was to evaluate the effects of needle flexor tendon tenotomy treatment of the diabetic hammertoe deformity. RESEARCH DESIGN AND METHODS A multicenter randomized controlled trial of individuals with diabetes and ulcers or impending ulcers associated with hammertoes was performed between 1 November 2019 and 31 March 2021. Participants were stratified by the presence of ulcers or impending ulcers. Participants were randomly assigned to tenotomy and standard nonsurgical treatment or to standard nonsurgical treatment alone. Primary outcomes were time to ulcer healing and progression from impending ulcer to active ulcer. RESULTS Of 224 screened participants with diabetes, 95 (59.0% men) were included. The mean follow-up was 291 ± 70 days, 28 (29.5%) had type 1 diabetes, mean diabetes (presented with 25–75% quartile) duration was 20 (13–26) years, and mean age was 67.7 ± 9.8 years. Of the included participants, 16 had ulcers, of whom 8 were randomly assigned to intervention. Of the remaining 79 with impending ulcers, 39 were randomly assigned to intervention. For participants with ulcers, healing rates favored tenotomy (100% vs. 37.5%, P = 0.026) as did time to ulcer healing (P = 0.04). For those with impending ulcers, incidence of progression to an active ulcer was lower (1 vs. 7, P = 0.028) and the number of ulcer-free days higher (P = 0.043) in the tenotomy group. No serious adverse events were recorded. CONCLUSIONS This randomized study showed that the simple procedure of needle flexor tendon tenotomy was effective and safe when treating and preventing ulcers associated with the diabetic hammertoe deformity.
Vitamin D Supplementation and the Incidence of Cataract Surgery in Older Australian Adults
Authors: Sabbir T. Rahman, Mary Waterhouse, Briony Duarte Romero, Catherine Baxter, Dallas English, David A. Mackey, Peter R. Ebeling, Bruce K. Armstrong, Donald S.A. McLeod, Gunter Hartel, Rachel L. O’Connell, Jolieke C. van der Pols, Alison J. Venn, Penelope M. Webb, David C. Whiteman, Rachel E. Neale
Journal: Ophthalmology (2022)
Health‐related quality of life in acute heart failure: association between patient‐reported symptoms and markers of congestion
Authors: Matthew M.Y. Lee, Ross T. Campbell, Brian L. Claggett, Eldrin F. Lewis, Kieran F. Docherty, Moritz Lindner, Jiankang Liu, Scott D. Solomon, John J.V. McMurray, Elke Platz
Journal: European Journal of Heart Failure (2022)
Collagen Niches Affect Direct Transcriptional Conversion toward Human Nucleus Pulposus Cells via Actomyosin Contractility
Authors: Kesi Shi, Chengzhen Liang, Xianpeng Huang, Shaoke Wang, Jiangjie Chen, Feng Cheng, Chenggui Wang, Liwei Ying, Zhaoqi Pan, Yuang Zhang, Jiawei Shu, Biao Yang, Jingkai Wang, Kaishun Xia, Xiaopeng Zhou, Hao Li, Fangcai Li, Yiqing Tao, Qixin Chen
Journal: Advanced Healthcare Materials (2022)

Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs). Next, tunable physical properties of collagen niches are fabricated based on various crosslinking degrees. Collagen niches significantly affect actomyosin cytoskeleton and then influence the maturation of iNPLCs. Using gain- and loss of function approaches, the appropriate physical states of collagen niches are found to significantly enhance the maturation of iNPLCs through actomyosin contractility. Moreover, in a rat model of degenerative disc diseases, iNPLCs with collagen niches are transplanted into the lesion to achieve significant improvements. As a result, overexpression of transcription factors in human dermal fibroblasts are efficiently converted into iNPLCs and the optimal collagen niches affect cellular cytoskeleton and then facilitate iNPLCs maturation toward human nucleus pulposus cells. These findings encourage more in-depth studies toward the interactions of niches and direct conversion, which would contribute to the development of direct conversion.
High Throughput Omnidirectional Printing of Tubular Microstructures from Elastomeric Polymers
Authors: Chuan Liu, Scott B. Campbell, Jianzhao Li, Dawn Bannerman, Simon Pascual‐Gil, Jennifer Kieda, Qinghua Wu, Peter R. Herman, Milica Radisic
Journal: Advanced Healthcare Materials (2022)

Bioelastomers are extensively used in biomedical applications due to their desirable mechanical strength, tunable properties, and chemical versatility; however, three-dimensional (3D) printing bioelastomers into microscale structures has proven elusive. Herein, a high throughput omnidirectional printing approach via coaxial extrusion is described that fabricates perfusable elastomeric microtubes of unprecedently small inner diameter (350-550 µm) and wall thickness (40-60 µm). The versatility of this approach is shown through the printing of two different polymeric elastomers, followed by photocrosslinking and removal of the fugitive inner phase. Designed experiments are used to tune the microtube dimensions and stiffness to match that of native ex vivo rat vasculature. This approach affords the fabrication of multiple biomimetic shapes resembling cochlea and kidney glomerulus and affords facile, high-throughput generation of perfusable structures that can be seeded with endothelial cells for biomedical applications. Post-printing laser micromachining is performed to generate micro-sized holes (520 µm) in the tube wall to tune microstructure permeability. Importantly, for organ-on-a-chip applications, the described approach takes only 3.6 min to print microtubes (without microholes) over an entire 96-well plate device, in contrast to comparable hole-free structures that take between 1.5 and 6.5 days to fabricate using a manual 3D stamping approach.
Enhancing anti-tumor effect of ultrasensitive bimetallic RuCu nanoparticles as radiosensitizers with dual enzyme-like activities
Authors: Bochuan Hu, Xiaohui Xiao, Pin Chen, Jieying Qian, Guotao Yuan, Yayi Ye, Lingli Zeng, Suqin Zhong, Xiaoli Wang, Xiaohua Qin, Yuedong Yang, Yue Pan, Yunjiao Zhang
Journal: Biomaterials (2022)
MoS2 nanoflower-mediated enhanced intratumoral penetration and piezoelectric catalytic therapy
Authors: Yaqian He, Zichuang Xu, Yuchu He, Guanghui Cao, Song Ni, Yongfu Tang, Jidong Wang, Yi Yuan, Zhenhe Ma, Desong Wang, Dawei Gao
Journal: Biomaterials (2022)
Recent advances in bacterial therapeutics based on sense and response
Authors: Zhuo Feng, Yuchen Wang, Haiheng Xu, Yunfei Guo, Wen Xia, Chenxuan Zhao, Xiaozhi Zhao, Jinhui Wu
Journal: Acta Pharmaceutica Sinica B (2022)

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.
Low utilization of adult-to-adult LDLT in Western countries despite excellent outcomes: International multicenter analysis of the US, the UK, and Canada
Authors: Tommy Ivanics, David Wallace, Marco P.A.W. Claasen, Madhukar S. Patel, Rushin Brahmbhatt, Chaya Shwaartz, Andreas Prachalias, Parthi Srinivasan, Wayel Jassem, Nigel Heaton, Mark S. Cattral, Nazia Selzner, Anand Ghanekar, Gabriela Morgenshtern, Neil Mehta, Allan B. Massie, Jan van der Meulen, Dorry L. Segev, Gonzalo Sapisochin
Journal: Journal of Hepatology (2022)
Genome assembly and annotation of <i>Periplaneta americana</i> reveal a comprehensive cockroach allergen profile
Authors: Lingyi Wang, Qing Xiong, Nawannaporn Saelim, Lin Wang, Wenyan Nong, Angel Tsz‐Yau Wan, Mai Shi, Xiaoyu Liu, Qin Cao, Jerome Ho Lam Hui, Nitat Sookrung, Ting‐Fan Leung, Anchalee Tungtrongchitr, Stephen Kwok Wing Tsui
Journal: Allergy (2022)

One of the most common cockroach types in urban areas, the American cockroach (Periplaneta americana), has been reported to impose an increased risk of allergies and asthma. Limited groups of allergens (Per a 1-13) have been identified in this species due to the lack of genome-related information.To expand the allergen profile of P. americana, genomic, transcriptomic, and proteomic approaches were applied. With the support of a high-quality genome assembled using nanopore, Illumina, and Hi-C sequencing techniques, potential allergens were identified based on protein homology. Then, using enzyme-linked immunosorbent assay, selected allergens were tested in Thai patients allergic to P. americana.A chromosomal-level genome of P. americana (3.06 Gb) has been assembled with 94.6% BUSCO completeness, and its contiguity has been significantly improved (N50 = 151 Mb). A comprehensive allergen profile has been characterized, with seven novel groups of allergens, including enolase (Per a 14), cytochrome C (Per a 15), cofilin (Per a 16), alpha-tubulin (Per a 17), cyclophilin (Per a 18), porin3 (Per a 19), and peroxiredoxin-6 (Per a 20), showing IgE sensitivity in enzyme-linked immunosorbent assay. A new isoallergen of tropomyosin (Per a 7.02) and multiple potential isoallergens of Per a 5 were revealed using bioinformatics and proteomic approaches. Additionally, comparative analysis of P. americana with the closely related Blattodea species revealed the possibility of cross-reaction.The high-quality genome and proteome of P. americana are beneficial in studying cockroach allergens at the molecular level. Seven novel allergen groups and one isoallergen in Per a 7 were identified.
Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma
Authors: Michael Heming, Svea Haessner, Jolien Wolbert, I-Na Lu, Xiaolin Li, Benjamin Brokinkel, Michael Müther, Markus Holling, Walter Stummer, Christian Thomas, Andreas Schulte-Mecklenbeck, Flavia de Faria, Marlon Stoeckius, Stephan Hailfinger, Georg Lenz, Kornelius Kerl, Heinz Wiendl, Gerd Meyer zu Hörste, Oliver M. Grauer
Journal: Genome Medicine (2022)

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare lymphoma of the central nervous system, usually of diffuse large B cell phenotype. Stereotactic biopsy followed by histopathology is the diagnostic standard. However, limited material is available from CNS biopsies, thus impeding an in-depth characterization of PCNSL. Methods We performed flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing of PCNSL cells released from biopsy material, blood, and cerebrospinal fluid (CSF), and spatial transcriptomics of biopsy samples. Results PCNSL-released cells were predominantly activated CD19 + CD20 + CD38 + CD27 + B cells. In single-cell RNA sequencing, PCNSL cells were transcriptionally heterogeneous, forming multiple malignant B cell clusters. Hyperexpanded B cell clones were shared between biopsy- and CSF- but not blood-derived cells. T cells in the tumor microenvironment upregulated immune checkpoint molecules, thereby recognizing immune evasion signals from PCNSL cells. Spatial transcriptomics revealed heterogeneous spatial organization of malignant B cell clusters, mirroring their transcriptional heterogeneity across patients, and pronounced expression of T cell exhaustion markers, co-localizing with a highly malignant B cell cluster. Conclusions Malignant B cells in PCNSL show transcriptional and spatial intratumor heterogeneity. T cell exhaustion is frequent in the PCNSL microenvironment, co-localizes with malignant cells, and highlights the potential of personalized treatments.
Antigen- and scaffold-specific antibody responses to protein nanoparticle immunogens
Authors: John C. Kraft, Minh N. Pham, Laila Shehata, Mitch Brinkkemper, Seyhan Boyoglu-Barnum, Kaitlin R. Sprouse, Alexandra C. Walls, Suna Cheng, Mike Murphy, Deleah Pettie, Maggie Ahlrichs, Claire Sydeman, Max Johnson, Alyssa Blackstone, Daniel Ellis, Rashmi Ravichandran, Brooke Fiala, Samuel Wrenn, Marcos Miranda, Kwinten Sliepen, Philip J.M. Brouwer, Aleksandar Antanasijevic, David Veesler, Andrew B. Ward, Masaru Kanekiyo, Marion Pepper, Rogier W. Sanders, Neil P. King
Journal: Cell Reports Medicine (2022)

Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.
Fellowships, Grants, Awards
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Fellowships, Grants, Awards Get access JNCI: Journal of the National Cancer Institute, Volume 87, Issue 24, 20 December 1995, Pages 1895–1896, https://doi.org/10.1093/jnci/87.24.1895 Published: 20 December 1995
Essays on Surgical Subjects.
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Accidental hypothermia.
Authors: P Le Conte, D Baron
Journal: BMJ (1966)

Accidental hypothermia is an important clinical condition in emergency and disaster medicine. It is usually classified as mild, moderate, severe, or extreme (body temperature below 18-20 degrees C; no recordable EEG activity). However, exposure time, trauma, serious illness, or the effects of drugs or alcohol may both attenuate and complicate the clinical course. This paper describes exposure mechanisms, the pathophysiologic processes, the body's thermo-regulating mechanism and diagnostic criteria. The author also discusses choice of treatment in the acute stages, during transportation and in hospital. The treatment should take into account not only the degree of hypothermia, but also exposure time, state of consciousness, and complicating factors such as trauma, drugs or alcohol. When hypothermia is associated with cardiac arrest, rewarming by extracorporal support is recommended.
Computers in Medicine
Authors: Donald A. B. Lindberg
Journal: JAMA (1995)

Since previous Contempo reports on computers in medicine in 1989 and 1990, computing systems and devices have been incorporated into medical practice at an accelerating rate. The influence of computing can be seen in diagnostic imaging systems, radiation therapy, the intensive care unit, the clinical laboratory, and the business office. Planning for institution-wide advanced information management systems has become more sophisticated and widespread.<sup>1</sup>The American Medical Informatics Association has been formed as a forum for open scientific meetings and education in the field of medical informatics. Virtually every US academic medical center and many hospitals have on-line or CD-ROM systems that allow individual health professionals and students to search MEDLINE and other databases for themselves. A rapidly growing group of institutions and individuals use Internet connections to reach information sources and to transmit and receive the full text of documents.<sup>2</sup>Many physician "end-users" search databases from home or